Formate metabolism and toxicity will be studied in methanol sensitive and methanol insensitive species. Ocular toxicity will be determined and means to promote and prevent lesions will be evaluated. Metabolic regulation will also be determined in isolated hepatocyte preparations from starved and fed rats, preparations which may simulate in vitro the in vivo response of the monkey and rat, respectively. Enzymologic studies on formyltetrahydrofolate synthetase, formyltetrahydrofolate dehydrogenase, dihydrofolate reductase and other possible regulating enzymes are planned. The objectives are to explain the species differences in methanol sensitivity on a biochemical basis. This information will allow for improved understanding of regulatory functions of the folate metabolic pathway.